The compound with triazabicyclo[3,2,1]octane structure has attracted great attention from chemists and medical experts because of its unique molecular structure.
Aplaminal is the first compound that is found to have triazabicyclo[3,2,1
octane structure, and was first separated by Takeshi Kuroda and Hideo Kigoshi et al. from Aplysia (Varria) kurodai in the year of 2008 (Org. Lett., Vol. 10, No. 3, p489-491, 2008). Its specific structure is as follows:

The literature characterizes the structure of Aplaminal through NMR and single crystal X-ray diffraction. It is reported that Aplaminal has the cytotoxicity against HeLa S3 cells (IC50=0.51 ug/mL). More clinical trials are still being researched. The preparation of Aplaminal through biological extraction involves extremely high cost and produces a very low yield. Generally, only 2 mg of Aplaminal can be extracted from 18 kg of aplysia. Therefore, Amos B. Smith III and Zhuqing Liu et al. (Org. Lett., Vol. 10, No. 19, p4363-4365, 2008) prepared Aplaminal through synthesis with N-Boc-(D)-serine as the raw material in 9 reaction processes, including hydroxyl protection, condensation, reduction, etc., obtaining a yield of 17%. The specific reaction process is as follows:

However, it is also very difficult to synthesize the compound with a triazabicyclo[3,2,1]octane structure. The above synthetic method of Aplaminal suffers from redundant reaction processes; expensive reagents such as diisobutylaluminum hydride (Dibal-H), Pd and Pt; difficult pilot process control; less safety and low yield; and is also not applicable for industrial production.
At present, there are many reports of other triazacyclo compounds. The patent document CN1864663 discloses the pharmaceutical compositions of 5,7,14-triazatetracyclo[10.3.1.0(2,11).0(4,9)]-hexadeca-2(11)3,5,7,9-pentaene. The patent document CN102282148A discloses 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene citrate salt. The patent document CN1509288 discloses the citrate salt of 5,8,14-triazatetracyclo[10.3.1.02,11.04,9]-hexadeca-2(11),3,5,7,9-pentaene. The patent document CN1509174 discloses the tartrate salt of 5,8,14-triazatetracyclo[10.3.1.02,11.04,9]-hexadeca-2(11),3,5,7,9-pentaene. The patent document CN1589148 discloses the succinic acid salts of 5,8,14-triazatetracyclo[10.3.1.0.2, 10.04,8]-hexadeca-2(11),3,5,7,9-pentaene and pharmaceutical compositions thereof. These patent documents all disclose such a chemical structure with triazatetracyclo.
Through careful research, the inventor has unexpectedly developed a simple, feasible and economic method of preparing a novel compound of triazabicyclo[3,2,1]octane structure using 5-methyltetrahydrofolate as the raw material. This compound has a significant effect on inhibiting T lymphocyte proliferation.